Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome
| Autor: | Fred S. Rosen, Maxim I. Lutskiy, Eileen Remold-O'Donnell, Diana S. Beardsley |
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| Rok vydání: | 2005 |
| Předmět: |
Wiskott–Aldrich syndrome
Genetic enhancement Immunology Gene Expression macromolecular substances Biology medicine.disease_cause Biochemistry Interleukin 21 medicine Humans Progenitor cell Child Immunobiology Mutation Base Sequence Mosaicism Wiskott–Aldrich syndrome protein Proteins Cell Biology Hematology medicine.disease Flow Cytometry Molecular biology Wiskott-Aldrich Syndrome Killer Cells Natural Haematopoiesis biology.protein Stem cell Wiskott-Aldrich Syndrome Protein |
| Zdroj: | Blood. 106(8) |
| ISSN: | 0006-4971 |
| Popis: | Rare cases of somatic mosaicism resulting from reversion of inherited mutations can lead to the attenuation of blood-cell disorders, including Wiskott-Aldrich syndrome (WAS). The impact of the revertant hematopoietic stem or progenitor cells, particularly their representation in blood-cell populations, is of interest because it predicts the outcome of gene therapy. Here we report an 8-year-old patient with WAS caused by a single nucleotide insertion in the WASP gene that abrogates protein expression. The patient nonetheless had mild disease. We found reversion of the mutation in a fraction of patient lymphocytes. Forty percent of natural killer (NK) cells expressed Wiskott-Aldrich syndrome protein (WASP), and NK cells contained both mutated and revertant (normal) sequences. WASP was not expressed in patient T or B cells; T cells contained only the mutated sequence. The selective advantage of WASP+ NK cells was also demonstrated for carrier females. The enrichment of WASP+-revertant NK cells indicates that WASP provides a selective advantage in this lineage and predicts the success of gene therapy for reconstituting the NK-cell compartment. The importance of reconstituting the NK-cell lineage is discussed. (Blood. 2005;106:2815-2817) |
| Databáze: | OpenAIRE |
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